It has been reported that (+)-5-(3,4-difluorophenyl)-5-[(3-methyl-2-oxopyridin-1(2H)-yl)methyl]imidazolidin-2,4-dione has an excellent inhibitory activity of a tumor necrosis factor alpha (TNF-α) converting enzyme (TACE) and is useful as a therapeutic and prophylactic agent for diseases involving TNF-α (Patent Literature 1).
In Patent Literature 1, the following two methods are disclosed as methods for producing the optically pure (+)-5-(3,4-difluorophenyl)-5-[(3-methyl-2-oxopyridin-1(2H)-yl)methyl]imidazolidin-2,4-dione.
(wherein X represents a chlorine atom, a bromine atom, or an iodine atom; and the asterisk (*) signifies an optically pure form)
(In the formulae, the asterisk (*) signifies an optically pure form)
The production method of scheme 1 is a method of optically dividing a racemate by chiral column chromatography, and from the viewpoint of production efficiency it is hard to say that this method is suitable for production on a commercial scale. In addition, in the production method of scheme 2, the (R)-tert-butanesulfinamide used as an asymmetric auxiliary group is expensive and it involves reactions that produce impurities that are difficult to remove, such as impurities derived from a titanium reagent, and hence from the viewpoint of manufacturing cost and work efficiency, it would be undesirable to apply this method on a commercial scale.